Glycoconjugates are major components of the outer surface of mammalian cells. During mammalian development, the carbohydrate structures of these glycoconjugates change dramatically. In many cases, specific sets of carbohydrates are characteristic for particular stages of differentiation. Where these specific carbohydrates are recognized by specific antibodies, the carbohydrate structures are useful as differentiation antigens (Feizi, Nature 314:51-55, (1985); Fukuda et al., J. Biol. Chem., 260:6623-6631 (1985), each of which is incorporated herein by reference). In the mature organism, expression of distinct carbohydrates ultimately is restricted to specific cell types and aberrations in the specific cell surface carbohydrates often are associated with malignant transformation of the cells (Hakomori, Ann. Rev. Immunol., 2:103-126 (1984)). Although the functional significance of alterations in cell surface carbohydrates during cell differentiation and in malignancy is not completely understood, several reports suggest that these molecules are involved in the modulation of adhesive processes.
It has been generally accepted that each glycosyltransferase catalyzes a single enzymatic reaction to form a specific linkage. One notable exception is the Lewis fucosyltransferase, which can synthesize both .alpha.1,3 and .alpha.1,4 linkages (Prieels et al., J. Biol. Chem. 256:10456-10463 (1981); Kukowska-Latallo et al., Genes & Devel. 4:1288-1303 (1990), each of which is incorporated herein by reference). A specific linkage usually is associated with the formation of specific oligosaccharides, which also may contain other linkages formed in conjunction with the action of other glycosyltransferases. Thus, the presence of specific oligosaccharides on the cell surface is the result of the coordinate expression of one or more glycosyltransferase genes responsible for synthesis of the oligosaccharide linkages. Recently, cDNAs encoding approximately a dozen different glycosyltransferases have been isolated (Paulson and colley, J. Biol. Chem., 264:17615-17618 (1989); Schachter, Curr. Opin. Struct. Biol., 1:755-765 (1991); Joziasse, Glycobiology 2:271-277 (1992)). However, little is known about the regulation of glycosyltransferases or glycosyltransferase gene expression during development and in malignancy.
Thus a need exists to identify and characterize members of the glycosyltransferase enzyme family. The present invention satisfies this need and provides related advantages as well.